Component separation device, method of producing the device, and method of separating component by using the device

ABSTRACT

A component separation device includes a substrate having a flow path formed therein and arranged to store a fluid containing a liquid component and a solid component, and an actuator causing the fluid stored in the flow path to vibrate. The actuator includes a first electrode provided on the substrate apart from the flow path, and a first piezoelectric member provided on the first electrode, and a second electrode provided on the first piezoelectric member. This separation device prevents the actuator from being contaminated by the fluid, and separates the components efficiently.

TECHNICAL FIELD

The present invention relates to a component separation device forseparating components from fluid including a liquid component and asolid component mixed therein, such as blood or emulsion, a method ofmanufacturing the device, and a method of separating components usingthe device.

BACKGROUND OF THE INVENTION

Fluid mixed with plural solid components, such as river water, seawater, or blood, are known. This fluid is mixture of liquid componentand solid components. The solid components, such as sand, bacteria, orblood corpuscle cells, exist as solid substances by precipitation ordispersion while not being dissolved in the liquid component.

As a method of separating the plural components, a device for separatingblood corpuscle from blood will be described. Blood is generally sampledas whole blood including blood plasma as the liquid component, bloodcorpuscle cells as the solid components, and other components. However,either only the blood corpuscle cell or only the blood plasma is oftenrequired for examining the blood.

For example, in order to examine a blood sugar level in blood, it isnecessary to measure blood sugar dissolved in a blood plasma. In orderto detect DNA, DNA is taken out from a white blood corpuscle cell inblood corpuscle. Therefore, in order to separate blood plasma and bloodcorpuscle components from whole blood sampled by a conventional method,the whole blood is put in a test tube, and a predetermined centrifugalforce is applied to it with a centrifugal machine. The components in thewhole blood in the test tube receive respective centrifugal forcescorresponding to the components, thereby being separated by thedifference of their masses.

Then, the blood plasma component is obtained by extracting supernatantfluid, and the blood corpuscle component is obtained from precipitate.Then, the separated components are subjected to predeterminedmeasurements in an examination process.

The conventional method using the centrifugal machine has the followingproblem. This method requires a certain amount of the sample, forexample, several milliliters to several tens milliliters of the wholeblood in the test tube. By this method, it is difficult to separate theliquid component or the solid component from a small amount of thesample.

A method of separating the solid component from a small amount of sampleusing a filter is disclosed in “Integrated vertical screen micro-filtersystem using inclined SU-8 structure” (Yong-Kyu Yoon, MEMS2003, Kyoto,pp. 227-230 published by IEEE). A porous filter filters blood corpuscleshaving sizes larger than a predetermined size, thereby separating bloodcorpuscles from a blood plasma component. In this method, the size andthe number of pores of the filter affect its separation characteristics.Therefore, the filter is designed optimally to the component to beseparated. For example, a meshed filter can be manufactured preciselyregarding the size and the number of the pores of the filter by exposinga light sensitive resist three-dimensionally.

In this conventional method employing the filter, the particle size ofthe solid component passing through the filter depends on a pressureapplied to fluid or powder fluid containing plural components mixedtherein passing through the filter. The solid component particles,particularly having plural sizes, are hardly separated by this method.In order to take out the predetermined particles, the sizes of the poresof the filters are determined to allow particles smaller than thepredetermined particles to pass through the pores. The predeterminedparticles are trapped by the filter, and thus, may clog the pores of thefilter, thereby preventing small particles from passing through.

Japanese Patent Laid-Open Publication No. 2001-525722 discloses a devicefor performing manipulation of particles suspended in fluid. This deviceincludes a duct for allowing a fluid containing particles suspendedtherein to flow, an ultrasonic transducer provided at a side of theduct, and a reflector provided at another side of the duct. Theultrasonic transducer is provided on a side surface of a flow path ofthe duct. The ultrasonic transducer contacts the inside of the duct. Inthis device, an acoustic standing wave which passes across the duct inits width direction is generated, and thereby, condenses the particlesto form one or more planer bands extending in parallel with the verticalaxis of the duct, thereby separating the particles, i.e., solidcomponents, from liquid component.

In this device, the acoustic standing wave allows the particles toconcentrate at predetermined positions in the fluid, and it is notnecessary to be anxious about clogging of a filter. However, sincecontacting the inside of the duct, the ultrasonic transducer may becontaminated by the fluid in the duct. Since the ultrasonic transducerforms a part of the duct, the duct is necessarily formed of flatsurfaces, hence causing a vibration surface of the ultrasonic transducerto be a plane surface. Therefore, acoustic waves generated by thetransducer are limited to plane waves. It is difficult to install anultrasonic actuator precisely to the side surface of the duct.

SUMMARY OF INVENTION

A component separation device includes a substrate having a flow pathformed therein and arranged to store a fluid containing a liquidcomponent and a solid component, and an actuator causing the fluidstored in the flow path to vibrate. The actuator includes a firstelectrode provided on the substrate apart from the flow path, and afirst piezoelectric member provided on the first electrode, and a secondelectrode provided on the first piezoelectric member.

This separation device prevents the actuator from being contaminated bythe fluid, and separates the components efficiently.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a perspective view of a component separation device accordingto Exemplary Embodiment 1 of the present invention.

FIG. 2 is a top view of the component separation device according toEmbodiment 1.

FIG. 3 is a top view of the component separation device according toEmbodiment 1.

FIG. 4 shows a voltage to be applied to an actuator of the componentseparation device according to Embodiment 1.

FIG. 5 is a perspective view of another component separation deviceaccording to Embodiment 1.

FIG. 6 is a cross-sectional view of the component separation device forillustrating processes for manufacturing the device according toEmbodiment 1.

FIG. 7 is a cross-sectional view of the component separation device forillustrating the processes for manufacturing the device according toEmbodiment 1.

FIG. 8 is a cross-sectional view of the component separation device forillustrating the processes for manufacturing the device according toEmbodiment 1.

FIG. 9 is a cross-sectional view of the component separation device forillustrating the processes for manufacturing the device according toEmbodiment 1.

FIG. 10 is a cross-sectional view of the component separation device forillustrating the processes for manufacturing the device according toEmbodiment 1.

FIG. 11 is a cross-sectional view of the component separation device forillustrating the processes for manufacturing the device according toEmbodiment 1.

FIG. 12 is a cross-sectional view of the component separation device forillustrating the processes for manufacturing the device according toEmbodiment 1.

FIG. 13 is a perspective view of a component separation device accordingto Exemplary Embodiment 2 of the invention.

FIG. 14 is a perspective view of another component separation deviceaccording to Embodiment 2.

FIG. 15 is a top view of the component separation device shown in FIG.14.

FIG. 16 is a top view of the component separation device shown in FIG.14.

REFERENCE NUMERALS

-   1 Substrate-   2 Flow Path-   3 Actuator-   5 Common Electrode-   6A Piezoelectric Member-   6B Piezoelectric Member-   7A Drive Electrode-   7B Drive Electrode-   8 Inlet Port-   9 Outlet Port-   10A Through-Hole-   10B Through-Hole-   11 Solid Component-   12 Liquid Component-   13 Resist Mask-   14 Resist Mask-   15 Resist Mask-   16 Actuator-   18 Electrode Layer-   19 Piezoelectric Layer-   20 Electrode Layer-   26 Substrate-   27 Flow Path-   28 Actuator-   29 Inlet Port-   30 Outlet Port

DETAIL DESCRIPTION OF THE PREFERRED EMBODIMENTS Exemplary Embodiment 1

FIG. 1 is a perspective view of a component separation device accordingto Exemplary Embodiment 1 of the present invention. Flow path 2 isformed in substrate 1 made of silicon. Fluid containing a solidcomponent and a liquid component mixed therein is put in inlet port 8and discharged from the outside of the device, and flows out from outletport 9 via flow path 2. That is, the fluid is stored in flow path 2.Through-holes 10A and 10B are formed in bottom surface 2A of flow path 2to reach surface 1A opposite to bottom surface 2A. Actuator 3 havinglongitudinal direction 3A is provided on upper surface 1B of substrate 1apart from flow path 2. Longitudinal direction 3A of actuator 3 isparallel with side surface 2B of flow path 2. Actuator 3 includes commonelectrode 5 of platinum provided on substrate 1, piezoelectric members6A and 6B of titanate acid zirconate provided on common electrode 5, anddrive electrode 7A of gold provided on piezoelectric member 6A, anddrive electrode 7B of gold provided on piezoelectric member 6B. Commonelectrode 5 and drive electrodes 7A and 7B may include at least one ofgold, chrome, titanium, and platinum. Actuator 3 generates a largemagnitude of vibration efficiently with a low voltage even having asmall size.

Since longitudinal direction 3A of actuator 3 extends in parallel withside surface 2B of flow path 2 continuing to surface 1B, actuator 3generates the vibration efficiently, as described later. Device shown inFIG. 1 includes two actuators 3 at the outside of respective sidesurfaces of flow path 2, however, may include a single actuator forgenerating the vibration.

A method of separating solid component and liquid component from fluidincluding the components mixed therein with using this componentseparation device will be described. FIGS. 2 and 3 are top views of thecomponent separation device.

First, fluid 101 containing solid component 11 and liquid component 12mixed therein is put into inlet port 8. Fluid 101 fills flow path 2, andthen, flow out from outlet port 9. Solid component 11 and liquidcomponent 12 of fluid 101 flow randomly when nothing is applied to them,as shown in FIG. 2.

A high-frequency voltage oscillating at a predetermined frequency isapplied to actuator 3. Common electrode 5 is maintained at apredetermined potential, such as 0V. FIG. 3 shows a circuit connected toactuator 3, and FIG. 4 shows high-frequency voltages Va and Vb appliedto drive electrodes 7A and 7B, respectively. 180-degree-phase shifter102 causes high-frequency voltages Va and Vb to shift each other inphase by 180 degrees. High-frequency voltages Va and Vb causespiezoelectric members 6A and 6B to vibrate, i.e., to expand and contractrepetitively, respectively, and the vibrations are transmitted tosubstrate 1 and reach flow path 2. High-frequency voltages Va and Vb arepreferably biased by bias voltage E from a DC power source, as shown inFIG. 4, so that a voltage between piezoelectric member 6A and commonelectrode 5 is not inverted, and a voltage between piezoelectric member6B and common electrode 5 is not inverted. This operation preventspiezoelectric members 6A and 6B from polarization relaxation due toapplication of inversed voltages, thus driving them stably andpreventing deterioration of their characteristics. DC bias voltage E maybe either positive or negative as long as the voltage betweenpiezoelectric member 6A and common electrode 5 is not inverted and thevoltage between piezoelectric member 6B and common electrode 5 is notinverted.

In flow path 2, a standing wave of vibration is generated underpredetermined conditions of the shape of flow path 2 and the frequencyof the vibration. When the standing wave is generated in flow path 2, asshown in FIG. 3, solid component 11 concentrates at nodes of thestanding waves, and flows in flow path 2 to form lines. FIG. 3schematically shows solid component 11 flowing in flow path 2 whileconcentrating at three nodes of the standing wave.

Through-hole 10A of substrate 1 is provided below a position where solidcomponent 11 flows intensively. Fluid 101 is drawn to the lower side ofsubstrate 1 from through-hole 10A, and solid component 11 can beobtained with a small amount of liquid component 12 from through-hole10A. Through-hole 10B of substrate 1 is provided at a position otherthan the position where solid component 11 flows intensively. Onlyliquid component 12 can be obtained by drawing fluid 101 fromthrough-hole 10B. Through-holes 10A and 10B function as a componentoutlet for taking out solid component 11 and liquid component 12 fromfluid 101, respectively. When only one of solid component 11 and liquidcomponent 12, for example, only solid component 11 is required, it isnot necessary to form through-hole 10B corresponding to the othercomponent, that is, liquid component 12. The sizes and the number ofthrough-holes 10A and 10B are not necessarily designed uniquely forseparating specific blood plasma and blood corpuscle, thus allowing thisdevice to be used comprehensively.

FIG. 5 is a perspective view of another component separation deviceaccording to Embodiment 1. As shown in FIG. 5, actuator 16 may beprovided on lower surface 1A of substrate 1. Actuator 16 can be providedbelow flow path 2 on lower surface 1A, thereby transmitting itsvibration efficiently.

A method of manufacturing the component separation device according toEmbodiment 1 shown in FIG. 1 will be described. FIG. 6 to FIG. 12 arecross-sectional views of the component separation device forillustrating processes for manufacturing the device.

First, as shown in FIG. 6, electrode layer 18 made of platinum is formedon substrate 1 made of silicon. Piezoelectric layer 19 made of titanicacid zirconate is formed on electrode layer 18. Electrode layer 20 madeof gold is formed on piezoelectric layer 19. Electrode layers 18 and 20are formed by an ordinary method, such as vacuum evaporation orspattering. Piezoelectric layer 19 made of titanic acid zirconate can beformed by spattering process, hydrothermal synthesis, or sol-gelprocess. Piezoelectric layer 19 formed particularly by the spatteringprocess is displaced stably with an excellent piezoelectriccharacteristics.

Next, resist mask 13 having a predetermined pattern is formed onelectrode layer 20, as shown in FIG. 7. Then, as shown in FIG. 8,electrode layer 20 is etched to provide drive electrodes 7A and 7Bseparated from each other. Then, as shown in FIG. 9, piezoelectric layer19 made of titanic acid zirconate is etched to form piezoelectricmembers 6A and 6B separated from each other. Then, resist mask 13 isremoved.

Next, as shown in FIG. 10, resist mask 14 having a predetermined patternis provided on electrodes 7A and 7B and on electrode layer 18, andelectrode layer 18 is etched to form common electrode 5. Resist mask 14is removed after the etching.

Then, as shown in FIG. 11, resist mask 15 having a predetermined patternis formed on electrodes 7A and 7B, on electrode layer 18, and on uppersurface 1B of substrate 1. Then, substrate 1 is etched to form flow path2 having inlet port 8 and outlet port 9 in substrate 1 of silicon. Then,resist mask 15 is removed. Substrate 1 made of silicone is etched by adry etching process to have a fine shape accurately. Dry etching withmixed gas containing gas for facilitating the etching and gas forrestraining the etching processes substrate 1 accurately, therebyallowing the device to have a small size.

Then, as shown in FIG. 12, resist mask 21 having a predetermined patternis formed on lower surface 1A of substrate 1, and then, substrate 1 isetched to form through-holes 10A and 10B in the bottom of flow path 2.Resist mask 21 is removed after the etching, thus providing thecomponent separation device according to Embodiment 1.

Since actuator 3 is provided on the upper surface of substrate 1, pluralcomponent separation devices can be obtained at once from a single waferefficiently by the above method similarly to a semiconductor process.

Actuators 3 and 16 do not contact the fluid in flow path 2, hence beingprevented from being contaminated by the fluid. Each of actuators 3 and16 has longitudinal direction 3A extending in parallel with side surface2B of flow path 2. The device according to Embodiment 1 can generatevibration in flow path 2 adequately without loss, thereby separatingcomponents efficiently.

In order to manufacture the component separation device shown in FIG. 5,the electrode layers and the piezoelectric layer are formed under lowersurface 1A of substrate 1.

Exemplary Embodiment 2

FIG. 13 is a perspective view of a component separation device accordingto Exemplary Embodiment 2 of the present invention. In this device, flowpath 27 formed in substrate 26 made of silicon has a width increasingmonotonically from inlet port 29 and decreasing monotonically from aportion having maximum width W1 toward outlet port 30. Maximum width W1of portion 27A of flow path 27 is larger than width W1 and width W2 ofinlet port 29 and outlet port 30, respectively. Plural actuators 28 areprovided around flow path 27. Actuators 28 apply various vibrations toflow path 27 having wide width W1 as to generate standing waves, therebyseparating components variously. Actuators 28 can be installed easilyaround flow path 27 having the large width, hence separating thecomponents efficiently.

FIG. 14 is a perspective view of another component separation deviceaccording to Embodiment 2. FIGS. 15 and 16 are top views of thecomponent separation device shown in FIG. 14. Substrate 31 is providedwith flow path 32 connected to inlet port 38, flow path 44 connected tooutlet port 39, and flow path 33 between flow path 32 and flow path 44formed therein. Width W32 of flow path 32 is smaller than width W33 offlow path 33. Width W33 of flow path 33 is three times width W32 of flowpath 32. Actuators 34 are provided along both outsides of flow paths 32and 33, respectively.

A method of separating the components using this component separationdevice will be described. When fluid 45 containing solid components 41and 42 having different sizes from each other and liquid component 43mixed therein is put in inlet port 32, solid components 41 and 42 aredispersed randomly regardless of their sizes, and fluid 45 flows, asshown in FIG. 15. Solid component 42 is smaller than solid component 41.

Actuators 34 apply a vibration having a wavelength twice width W32 offlow path 32 to fluid 45 of flow path 32. A standing wave of thevibration having a half-wavelength equal to width W32 is generated inflow path 32 at a basic mode, and forms single region R1 in which solidcomponents 41 and 42 flow intensively is formed in parallel with flowpath 32, as shown in FIG. 16.

Since extending to both outsides of flow path 33, actuators 34 generatesa standing wave of the vibration in flow path 33, and the standing wavehas a wavelength identical to that in flow path 32. Since the wavelengthof this standing wave is ⅔ times of width W33 of flow path 33, astanding wave of a three-time mode in a width W33 is generated in flowpath 33. As shown in FIG. 16, three regions R2, R3, and R4 in whichstationary components 41 and 42 flow intensively are formed in parallelwith flow path 33.

A solid component having a small size and a solid component having a lowdensity can hardly be affected by standing waves. Therefore, small solidcomponent 42 out of solid components 41 and 42 concentrating at regionR1 in flow path 32 is dispersed more than solid component 41 in regionR1 in flow path 32, as shown in FIG. 16. In flow path 33, regions R1 andR3 are closer to walls 33A of flow path 33 than region R2, and hence,solid component 42 flowed from flow path 32 concentrates moreintensively at regions R3 and R4 than at region R2. In other words, theregion of concentrated flow can be controlled by the sizes or density ofsolid components, and different solid components can be separatedefficiently from the liquid component. Solid components 41 and 42 andliquid component 43 can be taken out from through-holes 40A and 40B andflow path 44 similarly to the component separation device of Embodiment1 shown in FIG. 1.

In the device shown in FIG. 14, since width W33 of flow path 33 is treetimes width W32 of flow path 32, the standing wave of basic mode isgenerated in flow path 32, and the standing wave of three-time mode isgenerated in flow path 33 by the vibration generated by actuator 34,thereby forming regions R1 to R4 in which solid components flowintensively. Actuators different from each other may be provided at theoutside of the flow paths 32 and 33, respectively, to generatevibrations having wavelengths different from each other. Then, width W33of flow path 33 may not be three times width W32 of flow path 32. In thedevice according to Embodiment 2 shown in FIG. 14, it is not necessaryto provide actuators different from each other on the outside of flowpaths 33 and 32, and hence the component separation device can bemanufactured and used easily.

In the device shown in FIG. 14, actuators 34 are provided on both sidesof flow paths 33 and 34, respectively. The number of actuators 34 is notlimited to it, and may be any number as long as it can apply appropriatevibrations.

In the device shown in FIG. 14 according to Embodiment 2, actuator 34includes common electrode 35 on substrate 31, piezoelectric members 36A,36B on common electrode 35, drive electrodes 37A and 37B onpiezoelectric members 36A and 36B, and can be driven similarly toactuator 3 of Embodiment 1.

INDUSTRIAL APPLICABILITY

A component separation device according to the present invention canseparate efficiently components in fluid containing liquid component andsolid component mixed therein, such as blood or emulsion.

1. A component separation device comprising: a substrate having a firstsurface and a second surface opposite to the first surface, thesubstrate having a flow path formed in the first surface, the flow pathbeing arranged to store a fluid containing a liquid component and asolid component; an actuator causing the fluid stored in the flow pathto vibrate, the actuator including a first electrode provided on thesubstrate apart from the flow path, and a first piezoelectric memberprovided on the first electrode, and a second electrode provided on thefirst piezoelectric member; and an outlet for taking out one of theliquid component and the solid component in the fluid therefrom.
 2. Thecomponent separation device according to claim 1, wherein the substratehas an inlet port and an outlet port formed therein, the inlet portbeing connected to the flow path for putting the fluid into the flowpath, the outlet port being provided at the flow path for dischargingthe fluid from the flow path.
 3. The component separation according toclaim 1, wherein the first electrode of the actuator is provided on thefirst surface of the substrate.
 4. The component separation deviceaccording to claim 1, wherein the first electrode of the actuator isprovided on the second surface of the substrate.
 5. The componentseparation device according to claim 1, wherein the actuator generates astanding wave in the fluid stored in the flow path.
 6. The componentseparation device according to claim 1, wherein the actuator furtherincludes a second piezoelectric member provided on the first electrode,and a third electrode provided on the second piezoelectric member. 7.The component separation device according to claim 1, wherein the firstelectrode of the actuator comprises at least one of gold, chrome, titan,and platinum, wherein the second electrode of the actuator comprises atleast one of gold, chrome, titan, and platinum, wherein the thirdelectrode of the actuator comprises at least one of gold, chrome, titan,and platinum, and wherein the first piezoelectric member and the secondpiezoelectric member comprise titanic acid zirconate.
 8. The componentseparation device according to claim 1, wherein the flow path has aportion having a width larger than a width of the inlet port and a widthof the outlet port.
 9. The component separation device according toclaim 8, wherein the width of the flow path increases monotonically fromthe inlet port to the portion, and decreases monotonically from theportion to the outlet port.
 10. The component separation deviceaccording to claim 1, wherein the flow path has a side surfacecommunicating with the first surface of the substrate, and wherein eachof the first electrode, the second electrode, and the firstpiezoelectric member of the actuator has a longitudinal directionextending in parallel with the side surface of the flow path.
 11. Thecomponent separation device according to claim 1, wherein the substratehas a through-hole formed from the flow path to the second surface ofthe substrate, and the outlet comprising the through-hole.
 12. Thecomponent separation device according to claim 1, wherein the substratecomprises silicon.
 13. The component separation device according toclaim 1, wherein the first electrode of the actuator comprises at leastone of gold, chrome, titan, and platinum; wherein the second electrodeof the actuator comprises at least one of gold, chrome, titan, andplatinum; and wherein the first piezoelectric member comprises titanicacid zirconate.
 14. A method of manufacturing a component separationdevice, comprising: forming a first electrode layer on a substrate;forming a piezoelectric layer on the first electrode; forming a secondelectrode layer on the piezoelectric member; processing the firstelectrode layer, the piezoelectric layer, and the second electrode layerto have predetermined patterns as to provide an actuator; and forming aflow path in the substrate by etching.
 15. The method according to claim14, further comprising forming an inlet port and an outlet portconnected to the flow path in the substrate by etching.
 16. The methodaccording to claim 14, wherein said forming of the flow path in thesubstrate by etching comprises forming the flow path in the substrate bydry etching.
 17. The method according to claim 16, wherein said formingof the flow path in the substrate by dry etching comprises forming theflow path in the substrate by dry etching using mixture gas containinggas for facilitating etching and gas for restraining etching.
 18. Themethod according to claim 14, wherein the first electrode layercomprises at least one of gold, chrome, titan, and platinum, and whereinthe second electrode layer comprises at least one of gold, chrome,titan, and platinum.
 19. The method according to claim 14, wherein thepiezoelectric layer comprises titanic acid zirconate.
 20. A method ofseparating components, comprising: providing a component separationdevice which includes a substrate having a first surface and a secondsurface opposite to the first surface, the substrate having a flow pathformed in the first surface, and an actuator including a first electrodeprovided on the substrate apart from the flow path, first and secondpiezoelectric members provided on the first electrode, and second andthird electrodes provided on the first and second piezoelectric members,respectively; storing a fluid containing a liquid component and a solidcomponent in the flow path; causing the actuator to vibrate by applyinga first voltage between the first electrode and the second electrode,the first voltage oscillating and having a DC bias, and by applying asecond voltage between the first electrode and the third electrode, thesecond voltage oscillating and having a DC bias, the second voltageshifting in phase by 180 degrees from the first voltage; generating astanding wave in fluid stored in the flow path with a vibration of theactuator; and separating one of the solid component and the liquidcomponent from the fluid having the standing wave generated therein.